基于脂代谢PPARα-SREBP-1c-FAS通路探讨枳葛保肝降脂方防治酒精性肝病的机制*

作者：李忠婷1，李 志2,3，康 严1，刘 鹏2

单位：1.西南医科大学中西医结合学院，四川 泸州 646000； 2.西南医科大学附属中医医院，四川 泸州 646000； 3.中西医结合防治消化系统疾病泸州市重点实验室，四川 泸州 646000

引用：引用：李忠婷，李志，康严，刘鹏.基于脂代谢PPARα-SREBP-1c-FAS通路探讨枳葛保肝降脂方防治酒精性肝病的机制[J].中医药导报,2025,31(8):12-16,46.

DOI：10.13862/j.cn43-1446/r.2025.08.003

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摘要：

目的：基于过氧化酶体增殖物激活受体-α（PPARα）-固醇调节元件结合蛋白1c（SREBP-1c）-脂肪酸合酶（FAS）信号通路探讨枳葛保肝降脂方含药血清对酒精性肝病L-O2肝细胞的保护作用及其脂质代谢的机制。方法：将L-O2肝细胞接种于6孔板，贴壁后分为正常对照组、模型组（2.5%乙醇处理）、美他多辛组（美他多辛含药血清加2.5%乙醇处理）、枳葛保肝降脂方低剂量组（2.5%枳葛保肝降脂方含药血清加2.5%乙醇处理）、枳葛保肝降脂方中剂量组（5.0%枳葛保肝降脂方含药血清加2.5%乙醇处理）及枳葛保肝降脂方高剂量组（10.0%枳葛保肝降脂方含药血清加2.5%乙醇处理），24 h后测定各组细胞上清液中乳酸脱氢酶（LDH）、天冬氨酸氨基转移酶（AST）水平；定量聚合酶链反应（qPCR）、蛋白质印迹法（Western blotting）测定各组细胞内PPARα、SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达。结果：与正常对照组比较，模型组细胞上清液中LDH、AST含量显著升高（P<0.001）；PPARα mRNA及蛋白表达水平降低，SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达水平显著升高（P<0.001）；与模型组比较，枳葛保肝降脂方高剂量组和美他多辛组细胞上清液LDH、AST含量均明显下降（P<0.001），PPARα mRNA及蛋白表达水平显著升高，SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达水平显著下降（P<0.001）。结论：枳葛保肝降脂方对酒精性肝病的脂质代谢有改善作用，其机制可能与上调PPARα表达，减少SREBP-1c、FAS、Lipin-1表达以抑制肝细胞脂质积累有关。

关键词：酒精性肝损伤；枳葛保肝降脂方；PPARα-SREBP-1c-FAS信号通路；L-O2肝细胞；脂质代谢

Abstract：

Objective: To investigate the protective effect and lipid metabolism mechanism of the serum containing Zhige Baogan Jiangzhi Fang on L-O2 hepatocytes in alcoholic liver disease based on PPARα-SREBP-1c-FAS signaling pathway. Methods: L-O2 hepatocytes were inoculated in 6-well plates, and after wall attachment, they were divided into normal group, model group (2.5% ethanol treatment), positive control group (Metadoxine-containing serum plus 2.5% ethanol), Zhige Baogan Jiangzhi Fang low dose group (2.5% Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5% ethanol), Zhige Baogan Jiangzhi Fang medium  dose group (5.0% Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5% ethanol) and Zhige Baogan Jiangzhi Fang high  dose group (10.0% Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5% ethanol). Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels were measured in the supernatant of the cells of each group after 24 h. PPARα, SREBP-1c, FAS, Lipin-1 mRNA and protein expression were determined by qPCR and Western blotting in each group of cells. Results: Compared with the normal group, the levels of LDH and AST in cell supernatant increased in the model group (P<0.001); PPARα mRNA and protein expression levels were reduced, and the mRNA and protein expression levels of SREBP-1c, FAS, Lipin-1 increased (P<0.001). In comparison with the model group, the LDH and AST levels in the cell supernatant of the Zhige Baogan Jiangzhi Fang high dose group and the Metadoxine group were significantly decreased (P<0.001). PPARα mRNA and protein expression levels were significantly increased, and SREBP-1c, FAS,Lipin-1 mRNA and protein expression levels were significantly decreased (P<0.001). Conclusion: Zhige Baogan Jiangzhi Fang has an ameliorating effect on lipid metabolism in alcoholic liver disease, and its mechanism may be related to upregulating  PPARα expression and reducing SREBP-1c, FAS and Lipin-1 expression to inhibit lipid accumulation in liver cells.

Key words：alcoholic liver injury; Zhige Baogan Jiangzhi Fang; PPARα-SREBP-1c-FAS signaling pathway; L-O2 hepatocytes; lipid metabolism

发布时间：2026-01-06

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